The Analgesic Effect Of Dexmedetomidine On Acute Inflammatory Visceral Pain In Rats

We selected the dexmedetomidine as the research object in this study,and verified the dexmedetomidine in the rat spinal cord analgesic for inflammatory visceral pain from pre-receptors,receptors and post-receptors,and discussed parts of the analgesia mechanism in protein level.As a new molecular targets,we want to look for a new analgesic thought about non-opioid drugs.ObjectiveTo investigate the analgesic effect and the underlying mechanisms of dexmedetomidine on acute inflammatory visceral pain in rats.Methods1.The analgesic effects of dexmedetomidine on acute inflammatory visceral pain in ratsSixty male SD rats(6-8 week old)were randomly divided into 5 groups with 12 rats in each group: normal control group(C group),model group(N group),low dose dexmedetomidine group(D1 group),middium dose of dexmedetomidine group(D2 group),high dose of dexmedetomidine group(D3 group).Dexmedetomidine was intrathecal administration by puncture 15 min before modeling.Modeling by 10 ?L 10% formalin injected into the colon through anus.Then the pain was scored every 15 min till to 2 h post modeling.The heart rate of rats was determined with a digital animal ECG.The effect of dexmedetomidine on rat intestinal propulsion was examined by charcoal method.HE staining was performed to observe the effect of dexmedetomidine on the neurotoxicity of spinal cord of rats.ELISA method was used to test Ach,NA and AGM levels in the spinal cord slices incubation liquid.2.The mechanism of dexmedetomidine's analgesic effectThirty 6-8 week old male SD rats were randomly divided into 5 groups with 6 rats in each group: model group(M group),dexmedetomidine group(D group),dexmedetomidine + yohimbine group(Y group),dexmedetomidine + GF109203 X group(G group),and dexmedetomidine + idazoxan group(I group).Dexmedetomidine was intrathecal administration by puncture 15 min before modeling.Modeling by 10 ?L 10% formalin injected into the colon through anus.The pain was scored at 30 min after pain.Kill the rats 2h after modeling.Immunohistochemistry and Western blot were performed to detect the expression of PKC?,n NOS and PAR-2 in rat spinal dorsal horn neurons.3.Statistical methodStatistical analysis was performed using SPSS11.0 statistical software.Data are expressed as mean ± standard deviation(x ±s).One-way ANOVA was performed for multiple comparisons followed by Q test(Newman-Keuls method)post-hoc comparisons.Differences were deemed significant if P<0.05.Results1.15 min after modeling,the pain score of rats in model group was significantly higher than those in dexmedetomidine groups and reached a maximum.Then it decreased gradually in model group.It reached peak at 30 min after modeling in dexmedetomidine high,medium and low groups,and they were less dose dependently than model group.2.The heart rates of rats in all groups showed little difference than normal control group.3.The carbo medicinalis pro pulsive rate of model group was lower than that of control.They were higher in dexmedetomidine groups than model group in a dose-dependent manner.4.HE staining showed there were no obvious difference of cord neural injuries in high,medium and low dose dexmedetomidine groups in this study.5.120 min after modeling,Ach and NA increased but AGM decreased in model group compared with control group,Ach and AGM decreased but NA increased in model group compared with dexmedetomidine groups in a dose-dependent manner.6.30 min after modeling,the pain score of rats in Yohimbine and Idazoxan group model group had significantly differences than those in other groups.7.Immuno-histochemistry staining showed that the expression of PKC? and n NOS was strongly positive in model group.But they were lower in dexmedetomidine groups than that in model group.They were stronger in Yohimbine group and Idazoxan group than that in dexmedetomidine group.They were weaker in GF109203 X group than that in model group and dexmedetomidine group.8.Western blot showed that significantly decreased the expression of n NOS,PKC? and PAR-2,they were significantly increased in Yohimbine group.PKC? and PAR2 were higher in the Idazoxan group,but there were no significant difference in the expression of n NOS.There were no significant difference in the expression of n NOS and PAR2 between dexmedetomidine group and GF109203 X group.Conclusion1.Dexmedetomidine has analgesic effects on acute inflammatory visceral pain model of rat,and it delays the peak of pain;2.The analgesic effect of dexmedetomidine is mediated partly by alpha-2 adrenergic receptor and the imidazoline-2 receptor,but alpha-2 adrenergic receptor predominates in the analgesic action;3.The mechanisms of the analgesic effect of dexmedetomidine relate to the regulation of neurotransmitter levels,and the inhibition of n NOS,PKC ? and PAR-2 expression.